title: Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection.
abstract: In vivo and in vitro exposure to stimulants has been associated with increased levels of HIV infection in PBMCs. Among these lymphocyte subsets, quiescent CD4(+) T cells make up the majority of circulating T cells in the blood. Others and we have demonstrated that HIV infects this population of cells inefficiently. However, minor changes in their cell state can render them permissive to infection, significantly impacting the viral reservoir. We have hypothesized that stimulants, such as cocaine, may perturb the activation state of quiescent cells enhancing permissiveness to infection. Quiescent T cells isolated from healthy human donors were exposed to cocaine and infected with HIV. Samples were harvested at different time-points to assess the impact of cocaine on their susceptibility to infection at various stages of the HIV life cycle. Our data show that a 3-day exposure to cocaine enhanced infection of quiescent cells, an effect that appears to be mediated by σ1R and D4R. Overall, our results indicate that cocaine-mediated effects on quiescent T cells may increase the pool of infection-susceptible T cells. The latter underscores the impact that stimulants have on HIV-seropositive individuals and the challenges posed for treatment.
authors.affiliation: 1.David Geffen School of Medicine, 615 Charles E. Young Dr. S., BSRB 173, Mail Code 736322, Los Angeles, CA 90095, USA. dvatakis@ucla.edu; Twitter: https://twitter.com/vatakisd.
authors.forename: Sohn G
authors.initials: SG
authors.lastname: Kim
authors.forename: James B
authors.initials: JB
authors.lastname: Jung
authors.forename: Dhaval
authors.initials: D
authors.lastname: Dixit
authors.forename: Robert
authors.initials: R
authors.lastname: Rovner
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Baldwin
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Vatakis
mesh_terms: D003042:Cocaine / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism; D048348:Reverse Transcription / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*; D000097605:Sigma-1 Receptor
chemical_list: D003042:Cocaine; D012333:RNA, Messenger; D050638:Receptors, Dopamine D4; D017480:Receptors, sigma; D014764:Viral Proteins; D000097605:Sigma-1 Receptor
keywords: human immunodeficiency virus; life cycle; reservoir; stimulant abuse; σ1 and D4 receptors